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Molecular and cellular effectiveness of charged particles (light and heavy ions) and neutrons

Cel


Progress has been made in the following areas:

Cell inactivation experiments on V79 cells
Mutation induction
DNA double strand break induction
Comparison of the effectiveness of high and low dose rate irradiation with alpha-source
Biological effectiveness of fast neutrons.

At the low dose levels generally encountered in environmental and occupational exposure to high-LET radiations, only a very small fraction of the cells at risk are traversed by a particle and a much smaller fraction by two or more particles. To approach these conditions in experimental investigations, construction, technical developments and optimization of charged-particles microbeam facilities have engaged LNL as well as Gray Laboratory, Giessen and PSI groups.
The LNL accelerator technical staff have developed the LPM "microbeam facility" at the 2MV AN2000 Van de Graaff accelerator. They have carried out work on the focusing and controlling their beam systems, in order to increase performance, and for the optimization of a detector complex for single ion hits and of a fast beam switching system aimed to be used in the "single event" experiments.
Optimization of the charged-particle microbeam have been performed by the Gray Laboratory group, during the present contract period and the system is now in routine experimental use.

Inactivation curves of human TK6 lymphoblasts and K562 pro-erythroblasts irradiated with X-rays have been obtained by ISS group. Preliminary experiments with protons of 11 keV/µm on suspension growing K562 cells have also been performed, but a modification of the irradiation device in order to increase the efficiency of cell recovery from the filters appears necessary.

The Gray Laboratory group have studied the role of higher-order repeating structure of the DNA in determining the fragmentation patterns, after irradiation with low and high LET radiation. Using conventional and pulsed-field electrophoresis systems they have compared the molecular weight distributions for DNA from cells irradiated with X-rays or 3 MeV alpha-particles (110 keV/µm). Experimental results show an enhancement of fragments in the 0.2-10 kbp region in DNA from cells irradiated with alpha-particles in comparison to X-rays, particularly around 500 bp. The Gray Laboratory group has set up the single cell gel electrophoresis technique ("comet" assay) for use in conjunction with their counted charged-particle microbeam. Initial results have distinguished DNA damage levels in hit and non-hit cells exposed to a low fluence of alpha-particle.
The Pulsed Field Gel Electrophoresis (PFGE) technique has be set up at ISS laboratory and used in DNA dsb induction experiments after irradiation with X-rays an protons of 31 keV/µm.
Experiments with the microgel single cell electrophoresis ("comet") technique have been carried out at the ISS on V79 cells irradiated with X-rays, in view of its possible application to the study of DNA damage induced by charged particles, including application with the microbeam at LNL for single-particle, single cell studies.
A complementary approach to the problem of DNA damage evaluation, has been followed by the "Demokritos" group, performing the measurement of thermal transition A(260) changes and dielectric-condutivity changes induced on mammalian macromolecular DNA after irradiation with gamma rays and with alpha particles. Data from Thermal Transition Spectrophotometry revealed a dual dose dependence response of the helix to coil transition temperature, measured by the changes of A(260), i.e. the hydrogen bond disruption for buffered solutions of macromolecular DNA, after irradiation with gamma-rays or alpha-particles: in the low dose region, i.e. 0-10 Gy, a DNA helix stability seems to be present; at higher doses a gradually decreasing mode of helix stability is observed.
Dependence of the transition temperature on dose has also been studied measuring the changes in conductivity, i.e. changes that proceed the hydrogen bond disruption.

Particular effort have been devoted by MRC group in the analysis of Monte-Carlo simulated tracks of protons, deuterons and alpha-particles, in the region 20-30 keV/µm, for seeking microscopic features that may be responsible for their observed biological effectiveness. New high-accuracy data for particle (p, d, alpha) track-scoring statistics have been obtained but no simple property has been identified that simultaneously correlates well with the observed RBEs of both p and d or p and alpha.
"Demokritos" group has also been engaged, by Monte Carlo computer simulation, in the investigation of the physical and chemical processes (energy transport and deposition, ionisation distributions and the production of primary chemical species) connected with the interaction of charged particles (especially alpha) with water molecules. As result of this work, the group was able to develop accurate analytical LET-Energy and Range-Energy relations microdosimetric calculations for alpha-particles valid between 100 keV-10 MeV energy range.
Recently, it has been shown and confirmed by independent experiments, performed at different european laboratories (LNL, Legnaro-Italy; CRC-Gray Laboratory and MRC-Radiobiology Unit, England) that low energy protons are more effective in inducing cell inactivation and mutation than other heavier charged ions (alpha) in the 10-35 Kev/micron LET region. These results have substantial implications for understanding the mechanisms of radiation action and the risk assessment for occupational and enviromental exposure to neutrons and alpha-particles. More recently, deuteron beams have been used to extend the earlier proton LET range to higher LET values. This project will extend the existing data (studies) on the biological effectiveness of different charged particles (light and heavy ions) and neutrons in inducing molecular and cellular damage. In particular it is proposed to perform direct comparison of protons/deuterons with helium ions of similar LET values ; analysis of the effectiveness of a representative set of heavy ions(Li, B, C, N, 0 and P) as well as of fast neutrons in inducing cell inactivation and mutation; determination of the initial yield of DNA double strand break in cells irradiated with protons/deuterons and helium ions of similar LET values; study of the effectiveness of a single (and few) proton, deuteron and alpha particle to induce in a single cell inactivation, mutation and DNA damage; development and use of different assays for the detection of the distribution of DNA lesions. The particle beams available at the Van de Graaff accelerators of
the INFN-Legnaro in Italy, of the Gray Laboratory in England and Demokritos in Greece will be used. Facility for cell irradiation with heavy ions will be set-uP. As far as the single event is concerned the opportunity provided by the "microbeam" facilities at INFN-LNL in Italy and at Gray Laboratory in England will be exploited. analysis of microscopic track structure of the radiations will be performed to seek features which correlate their observed biological effectiveness. The present project will be advantaged for the already existing link among the partecipant groups and for the mutual interchanges of experiences and information.

Dziedzina nauki

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CSC - Cost-sharing contracts

Koordynator

ISTITUTO NAZIONALE DI FISICA NUCLEARE
Wkład UE
Brak danych
Adres
Via Romea 4
35020 LEGNARO
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Ostatnia aktualizacja: 26 Lutego 1993

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Permalink: https://cordis.europa.eu/project/id/FI3P0053/pl

European Union, 2024